Laryngoonychocutaneous syndrome

Overview

Laryngoonychocutaneous syndrome (LOC syndrome), also known as Shabbir syndrome, is an extremely rare autosomal recessive genetic disorder primarily affecting the mucous membranes, skin, nails, and larynx. It is most commonly reported in individuals of Punjabi origin and typically presents in infancy. The condition is characterized by chronic ulceration and granulation of mucosal surfaces, abnormal nail development, and skin lesions. One of the most serious complications is laryngeal involvement, which can lead to breathing difficulties and life-threatening airway obstruction.

Causes

Laryngoonychocutaneous syndrome is caused by mutations in the LCN1 gene (also known as LPHN1 or LCN1A1 in some sources), which encodes a protein known as lipocalin-1. This protein is believed to play a role in epithelial cell function and repair. The condition follows an autosomal recessive inheritance pattern, meaning a child must inherit two defective copies of the gene (one from each parent) to develop the syndrome. Consanguinity (marriage between relatives) increases the risk of this condition in affected populations.

Symptoms

The signs and symptoms of LOC syndrome generally appear within the first few months of life and include:

• Laryngeal granulation tissue – leading to hoarseness, stridor, and potential airway obstruction

• Oral and ocular ulcers – chronic granulation tissue affecting the conjunctiva and oral mucosa

• Abnormal nail development – thickened, dystrophic, or absent nails (particularly toenails)

• Skin lesions – including chronic erosions and areas of granulation tissue, often in periorificial areas

• Feeding difficulties – due to oral lesions and discomfort

• Potential visual impairment – due to conjunctival involvement and scarring

Diagnosis

Diagnosis of laryngoonychocutaneous syndrome is based on clinical evaluation, family history, and confirmatory genetic testing. Diagnostic approaches may include:

• Clinical examination – identifying characteristic mucocutaneous lesions and nail abnormalities

• Laryngoscopy – to detect granulation tissue in the airway

• Ophthalmologic evaluation – to assess ocular involvement and prevent vision loss

• Skin or mucosal biopsy – may reveal non-specific granulation tissue

• Genetic testing – to identify mutations in the LCN1 gene

Treatment

Treatment for LOC syndrome is primarily symptomatic and supportive, aimed at managing the chronic mucocutaneous issues and preventing complications. Management may include:

• Surgical removal of laryngeal granulation tissue – to maintain a patent airway

• Topical and systemic corticosteroids – to reduce inflammation and granulation

• Antibiotic and antiseptic treatments – to prevent or treat secondary infections

• Ophthalmologic care – including lubricants and surgical interventions to preserve vision

• Nutrition support – to address feeding difficulties in infants and young children

• Regular monitoring – by a multidisciplinary team including ENT, dermatology, ophthalmology, and pediatrics

Prognosis

The prognosis of laryngoonychocutaneous syndrome varies depending on the severity of symptoms and the timeliness of interventions. Early recognition and management of airway complications are crucial for survival. With proper care, some affected individuals can live into adulthood, although they may continue to experience recurrent mucosal issues and require multiple surgical interventions. Visual impairment and chronic skin lesions can affect quality of life, emphasizing the need for long-term follow-up and supportive care.